Lithium Carbonate in Treating Patients With Acute Intestinal Graft-Versus-Host-Disease (GVHD) After Donor Stem Cell Transplant

Not Applicable

Completed

Conditions: Noncontiguous Stage II Mantle Cell Lymphoma
Noncontiguous Stage II Marginal Zone Lymphoma
Noncontiguous Stage II Small Lymphocytic Lymphoma
Previously Treated Childhood Rhabdomyosarcoma
Primary Myelofibrosis
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma

Interventions: Drug: lithium carbonate
Other: laboratory biomarker analysis

Registration Number: NCT00408681

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: RATIONALE: Lithium carbonate may be an effective treatment for intestinal graft-versus-host disease caused by a donor stem cell transplant.

PURPOSE: This clinical trial is studying lithium carbonate in treating patients with acute intestinal graft-versus-host-disease after donor stem cell transplant.

Detailed Description: PRIMARY OBJECTIVES:

I. To evaluate the effects of lithium on functional and mucosal anatomic recovery in the small or large bowel of patients with acute GVHD.

II. Functional recovery will be evaluated according to changes in clinical manifestations of gastrointestinal GVHD. III. Mucosal anatomic recovery will be evaluated by review of results from clinically indicated endoscopic evaluations.

SECONDARY OBJECTIVES:

I. To assess the tolerability of lithium administration in allogeneic hematopoietic cell transplant recipients.

OUTLINE: Patients receive oral lithium carbonate once or twice daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Patient with a diagnosis of severe intestinal GVHD that is not improving at any time after initial treatment with glucocorticoids for at least 7 days are eligible for enrollment; measures indicating severity of GVHD will include: a) persistent diarrhea with average daily stool volumes > 500 mL per day; or b) persistent hemorrhage that is detectable by visual inspection of the stool
Patients with denuded mucosa caused by GVHD are eligible for enrollment, regardless of prior treatment for acute GVHD; denuded mucosa is defined as loss (i.e., erosion or sloughing) of the epithelium in: a) at least one-third of the surface area in a 30 cm colonic segment (i.e., rectosigmoid, descending or transverse colon); or b) at least one fifth of the surface area of the second portion of the duodenum, as estimated by endoscopic evaluation; denuded mucosa must be documented by images of the duodenum and colon and by histologic evaluation of the colon
All subjects must provide written informed consent with the use of forms approved by the Fred Hutchinson Cancer Research Center (FHCRC) Institutional Review Board (IRB)

Exclusion Criteria

Significant renal dysfunction (estimated creatinine clearance < 30 mL/min)
Persistent or recurrent malignancy
Secondary malignancy
Patients who had autologous or syngeneic marrow transplantation
Presence of any cause of intestinal symptoms or ulceration other than GVHD
Patients with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol will be excluded

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	laboratory biomarker analysis	Patients receive oral lithium carbonate once or twice daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.
Arm I	lithium carbonate	Patients receive oral lithium carbonate once or twice daily. Treatment continues for up to 8 weeks in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Functional Recovery	at 28 days after starting treatment with the study product	Functional recovery was defined as partial or complete resolution of gastrointestinal manifestations of acute graft-versus-host disease. Gastrointestinal manifestations of acute graft-versus-host disease include anorexia, nausea, vomiting, diarrhea, abdominal pain and bleeding. Complete response (CR) of intestinal GVHD was defined as the absence of any symptoms referable to intestinal GVHD. Partial response (PR) was defined as clearing of abdominal pain (or withdrawal of opioid analgesic requirements in patients treated for abdominal pain) and of grossly visible bleeding if present, and resolution of diarrhea or decrease in the three day average stool volume by ≥ 500 mL in patients with stool volumes of ≥ 500 mL. Progression of GVHD was defined as an increase in the three day average stool volume by \> 500 mL, or the development of new abdominal pain (or new opioid analgesic requirements) or new intestinal bleeding.

Secondary Outcome Measures

Name	Time	Method
Duration of Treatment With the Study Product	Up to 6 months	Number of days from beginning of orally administered lithium carbonate to the end of orally administered lithium carbonate
Recurrent or Progressive Malignancy	2 years after enrollment	Recurrence or progression of the malignant disease that was the reason for hematopoietic cell transplantation
Non-relapse Mortality	2 years after enrollment	Death without prior recurrent or progressive malignancy after transplantation.
Survival	2 years after enrollment	Patients who were alive at the specified time point
Causes of Death	up to 6 years after enrollment	Medical condition that made the greatest contribution in causing death
Mucosal Anatomic Recovery	9 to 11 weeks after starting treatment with the study product	Endoscopic evaluation of improvement. Categories include 1) no improvement, 2) regenerative changes, 3) limited improvement, 4) partial improvement and 5) complete response. Endoscopic manifestations of acute graft-versus-host disease include edema, erythema, mucosal ulceration and denudation. Complete mucosal recovery was defined as the appearance of intact mucosa with at least 98% of the luminal surface covered by epithelium. Partial response was defined as the appearance of mostly intact mucosa with at least 80% improvement or less than 10% denuded. Limited response was retrospectively designated to describe visible improvement that was less than partial response. Regenerative change was retrospectively designated to describe early reappearance of mucosal integrity in a previously denuded area but not sufficient to meet criteria for partial response. Failure to respond was defined as failure to meet partial response criteria.